Resp 7 - Lung cancer pathology

Question 1

What are common symptoms of lung cancer?

Answer 1

Haemoptysis
Cough (>3 weeks)
Chest/Shoulder Pain

Question 2

How can samples be acquired for cytological analysis?

Answer 2

• Bronchoscopy & Endobronchial Ultrasounds (EBU)

- Trans-thoracic CT scan

Question 3

What are the 2 major types of lung cancers?

Answer 3

• Non small cell cancer
• Small cell cancer
  –> first step on diagnosis is to determine which cell type it is with biopsy
  Sample the highest stage area as it is the most representative.

Question 4

What is TNM classification?

Answer 4

Tumour Nodes Metastases 
T1a -> <10 mm tumour 
The larger the number, the most extensive it is. T3 invades organs - diaphragm/heart.
N1/N2/N3 
M1a - spread to other lung 
M1b - brain

Question 5

What is SVCO?

Answer 5

Constriction of SVC caused by metastases.

Medical emergency.

Question 6

What are the 3 main aetiology of lung cancer?

Answer 6

• smoking
• asbestos
• radiation (therapeutic, radon)

Question 7

How do carcinoma develop from healthy cells?

Answer 7

Metaplasia -> dysplasia -> carcinoma in situ -> invasive carcinoma

Question 8

What are the three types of non-small cell carcinoma? What percentage of lung cancers are non-small cell?

Answer 8

• Squamous cell carcinoma
• Adenocarcinoma
• Large cell carcinoma
  80 % of lung cancers

Question 9

How are the incidences of squamous cell carcinoma and adenocarcinoma changing?

Answer 9

Squamous cell carcinoma incidence is decreasing

Adenocarcinoma incidence is increasing

Question 10

Where do squamous cell carcinomas and adenocarcinomas tend to arise?

Answer 10

Squamous cell carcinoma tends to arise near the mediastinum (airways). Ciliated epithelium changes to squamous epithelium because of repeated agression.
Adenocarcinoma tends to arise near the periphery. Forms from glandular epithelium..

Question 11

Why has a precursor lesion for small cell lung carcinoma not been found?

Answer 11

Because small cell carcinoma grows too quickly and it metastasises early

Question 12

How do the cells lining the airways change in squamous cell carcinoma?

Answer 12

The ciliated cells undergo metaplasia due to the chronic stimulation by cigarette smoke to become squamous cells

Question 13

Which type of lung cancer is common in non-smokers?

Answer 13

Adenocarcinoma

Question 14

Which types of lung caner are strongly associated with smoking?

Answer 14

Small cell carcinoma

Squamous cell carcinoma

Question 15

Describe the cytological features of squamous cell carcinoma.

Answer 15

Large Nuclei

Keratin in cytoplasm

Question 16

What is the precursor lesion for adenocarcinoma?

Answer 16

Atypical adenomatous hyperplasia = proliferation of atypical cells lining the alveolar walls. Increases in size and can eventually become invasive.

Question 17

At what point does adenocarcinoma in situ become invasive adenocarcinoma?

Answer 17

When the cells develop a mutation to produce enzymes so that they can break down the stroma and become invasive. The breaking down of the stroma causes inflammation and leads to the formation of fibrous tissue.

Question 18

Describe the cytological features of adenocarcinoma.

Answer 18

Adenocarcinoma shows glandular differentiation. They have big atypical nuclei with mucin globules

Question 19

What are the two molecular pathways for adenocarcinoma and which one is associated with smoking?

Answer 19

Smoker = K ras mutation 
Non-smoker = EGFR (Epidermal Growth Factor Receptor) mutation/amplification

Question 20

Why is it important to differentiate between the different pathways?

Answer 20

K ras mutation are not going to respond to targeted therapy (like Tarceva)
If EGFR, need to see if it is a responder or resistance mutation.
Responder can show almost complete regression with targeted therapies even with advanced disease.

Question 21

What is large cell carcinoma?

Answer 21

Poorly differentiated tumours composed of LARGE cells.
No histological evidence of glandular or squamous differentiation.
Probably poorly differentiated adenocarcinomas or squamous.
Poorer prognosis.

Question 22

What are the cytological features of small cell carcinoma?

Answer 22

Small, poorly differentiated cells (all effort put into proliferating, not differentiating, very fast proliferation). Grow so fast -> outgrow blood supply -> becomes necrotic.
Just nuclei with very small cytoplasm, kind of looks like lymphocytes.
Awful prognosis, worst type of lung cancer.

Question 23

What type of receptor is EGFR and what is used to block this receptor?

Answer 23

Membrane receptor tyrosine kinase

-> tyrosine kinase inhibitor

Question 24

What are paraneoplastic syndromes?

Answer 24

= systemic effect of tumour due to abnormal expression by tumour cells of factors (eg. hormones) not normally expressed by the tissue which the tumour arose.

Question 25

State some endocrine paraneoplastic syndromes.

Answer 25

ADH
-> syndrome of inappropriate ADH

ACTH
Cushing’s syndrome

Parathyroid hormone-related peptides
Hypercalcaemia

Others
Calcitonin -> hypocalcaemia
Gonadotrophins -> gynaecomastia